3358-17-6Relevant academic research and scientific papers
Short synthesis of 5-substituted-2,3,4,5-Tetrahydro-Benzo[f][1,4] Thiazepines by using a modified pictet-spengler reaction
Saitoh, Toshiaki,Kitabatake, Michikazu,Sugihara, Yuuko,Ono, Yuuki,Horiguchi, Yoshie,Mohri, Kunihiko
, p. 1063 - 1073 (2017)
5-Substituted-2,3,4,5-tetrahydrobenzo[f][1,4]thiazepines (6) were synthesized using a modified Pictet-Spengler reaction of N-formyliminium ion (4) as the key step. The cyclization of 4 was found to be affected by the acidity of the reaction media, which depended on the structure of the benzene ring. The cyclization of the substrates (4a-g) lacking an electron-donating substituent at the benzene ring proceeded smoothly by using a mixed acid catalyst of trifluoroacetic acid and a small amount of trifluoromethanesulfonic acid, thus giving N-formylbenzothiazepines (5a-g) in good yields. On the other hand, in the case of substrates (4h-j) with the OMe group at the benzene ring, although the cyclization proceeded by use of trifluoroacetic acid as the sole catalyst to give the products (5h-j), the mixed acid catalyst did not induce the cyclization reaction to any extent. The modified Pictet-Spengler reaction, which constitutes imination of 2-(phenylthio)ethanamine (1a) with aldehydes (2), and formylation of the resulting imines (3), followed by the acid-catalyzed cyclization of N-formyliminium ion (4), could be carried out as a one-pot procedure, thus providing a convenient methodology for synthesizing various 5-substituted-2,3,4,5-tetrahydrobenzo[f][1,4]thiazepines (6).
